Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes

Acta Diabetol. 2018 Mar;55(3):287-294. doi: 10.1007/s00592-017-1091-x. Epub 2018 Jan 11.

Abstract

Aims: To assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset.

Methods: The study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine.

Results: The autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (Rs - 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0-5.94), p = 0.04].

Conclusions: Children are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.

Keywords: Adult type 1 diabetes; Autoantibodies to zinc transporter-8; Autoimmune diabetes diagnosis; Autoimmunity; Childhood type 1 diabetes; Diabetes-related autoantibodies.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aging / blood
  • Aging / immunology*
  • Autoantibodies / blood*
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetic Ketoacidosis / blood
  • Diabetic Ketoacidosis / epidemiology
  • Energy Metabolism / physiology*
  • Female
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Seroepidemiologic Studies
  • Zinc Transporter 8 / immunology*

Substances

  • Autoantibodies
  • Biomarkers
  • SLC30A8 protein, human
  • Zinc Transporter 8